Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen

Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (A...

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Veröffentlicht in:PloS one 2015-02, Vol.10 (2), p.e0117778-e0117778
Hauptverfasser: Rampazo, Eline V, Amorim, Kelly N S, Yamamoto, Marcio M, Panatieri, Raquel Hoffmann, Rodrigues, Mauricio M, Boscardin, Silvia B
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Amorim, Kelly N S
Yamamoto, Marcio M
Panatieri, Raquel Hoffmann
Rodrigues, Mauricio M
Boscardin, Silvia B
description Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (ASP-2) to identify a region of this protein recognized by specific T cells. The hybrid αDEC-ASP2 mAb was successfully generated and preserved its ability to bind the DEC205 receptor. Immunization of BALB/c mice with the recombinant mAb in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)) specifically enhanced the number of IFN-γ producing cells and CD4+ T cell proliferation when compared to mice immunized with a mAb without receptor affinity or with the non-targeted ASP-2 protein. The strong immune response induced in mice immunized with the hybrid αDEC-ASP2 mAb allowed us to identify an ASP-2-specific CD4+ T cell epitope recognized by the BALB/c MHCII haplotype. We conclude that targeting parasite antigens to DCs is a useful strategy to enhance T cell mediated immune responses facilitating the identification of new T-cell epitopes.
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In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (ASP-2) to identify a region of this protein recognized by specific T cells. The hybrid αDEC-ASP2 mAb was successfully generated and preserved its ability to bind the DEC205 receptor. Immunization of BALB/c mice with the recombinant mAb in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)) specifically enhanced the number of IFN-γ producing cells and CD4+ T cell proliferation when compared to mice immunized with a mAb without receptor affinity or with the non-targeted ASP-2 protein. The strong immune response induced in mice immunized with the hybrid αDEC-ASP2 mAb allowed us to identify an ASP-2-specific CD4+ T cell epitope recognized by the BALB/c MHCII haplotype. We conclude that targeting parasite antigens to DCs is a useful strategy to enhance T cell mediated immune responses facilitating the identification of new T-cell epitopes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25679777</pmid><doi>10.1371/journal.pone.0117778</doi><oa>free_for_read</oa></addata></record>
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subjects Adenoviruses
Animals
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - metabolism
Antibody Formation
Antigenic determinants
Antigens
Antigens, Protozoan - chemistry
Antigens, Protozoan - genetics
Antigens, Protozoan - immunology
Breast cancer
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell activation
Cell proliferation
Chagas Disease - immunology
Chagas Disease - metabolism
Cloning
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Deoxyribonucleic acid
Disease Models, Animal
DNA
Epitopes
Epitopes, T-Lymphocyte - immunology
Female
Genes
HEK293 Cells
Humans
Immune response
Immune system
Immunization
Immunodominance
Immunodominant Epitopes - immunology
Infections
Information technology services
Interferon
Laboratories
Leishmania major
Lymphocytes
Lymphocytes T
Mice
Monoclonal antibodies
Neuraminidase - genetics
Neuraminidase - immunology
Parasitology
Peptides - immunology
Poly (I:C)
Polyinosinic:polycytidylic acid
Protein Binding - immunology
Proteins
Protozoa
Receptors
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
Recombinant Fusion Proteins - metabolism
Science
T cell receptors
T cells
Trypanosoma cruzi
Trypanosoma cruzi - immunology
Vaccines
Yersinia pestis
γ-Interferon
title Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen
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